PROJECT SUMMARY/ABSTRACT The overarching objective of this DDRCC is to foster and facilitate research in inflammatory bowel diseases (IBD) and related inflammatory diseases of the bowel. This theme has defined our GI program for 75 years, ever since Dr. Joseph B. Kirsner, the founder of modern gastroenterology at the University of Chicago, put forward the hypothesis that inflammatory bowel diseases are caused by combination of genetic, immunological, and microbial factors. We now know this is indeed the case, but recognize that other factors associated with recent changes in environment, lifestyle, and diet, are contributing to the increased prevalence and incidence of these diseases. The DDRCC has been the foundation of IBD research at the University of Chicago allowing us to build a highly collaborative, multidisciplinary team, a fully integrated translational research infrastructure, and state-of-the-art core facilities and services. In addition, the DDRCC has partnered with two University of Chicago affiliates, Argonne National Laboratory (ANL) and the Marine Biological Laboratory (MBL) at Woods Hole, to attract new investigators to the field and leverage their resources, talent, and facilities for the investigation of inflammatory diseases of the bowel. The central hypothesis of the collective group is that IBD and related inflammatory diseases of the bowel arise from a confluence of host, microbial, immunological, and environmental factors. The program is now in its 24th year, and, despite being a highly focused research program, the research base has steadily increased to 51 full and 16 associate member investigators with a total annual direct cost funding for digestive diseases of $14.8 million, of which ~$5.7 million comes from NIDDK (21% increase from 2009). The program has 4 major interrelated research themes that focus on the etiopathogenesis of IBD: (1) host immune/tissue responses, (2) the gut microbiome, (3) host genetics and gene function, and (4) environmental modifiers. The 4 DDRCC cores embracing these themes have continuously evolved to meet the needs of investigators and to anticipate new trends and technologies in biomedical research. The DDRCC has received tremendous institutional support as 1 of 5 priority areas designated for development by the Division of Biological Sciences. The DDRCC has successfully supported new investigators, but also drawn in talented scientists outside of the field of digestive diseases (15 now full members since 2010). Over the past two funding cycles, the P&F program has resulted in over $25M in extramural funds, or a 25 to 1 return-on-investment. Over the past funding cycle, 56% of the 306 publications acknowledging the DDRCC for its support were coauthored by two or more DDRCC members, indicating a high level of collaborative science. The number of high impact papers (Impact factor>20) published by DDRCC members has nearly doubled compared to the previous funding cycle. Thus, the DDRCC has successful met its goals of advancing the science and translation of discovery in inflammatory diseases of the bowel. The DDRCC as a whole is greater than the sum of its parts. It provides strategic vision, cutting-edge, high quality, and cost-effective services and resources, and gives opportunity to current and next generation scientists to flourish in a highly collaborative and productive environment.